DESCRIPTION, OVERALL (provided by applicant): The University of Alabama at Birmingham (UAB) Hepato/Renal Fibrocystic Diseases Core Center (UAB HRFDCC) will expand our previous P30-funded, interdisciplinary center of excellence in recessive PKD related research, to encompass ARPKD, as well as other single-gene disorders that comprise the hepato/renal fibrocystic diseases spectrum. The UAB HRFDCC will provide the impetus and the engine necessary to drive innovation, training, productivity, and new discovery within a North American network of investigators focused on this spectrum of disorders. The participating faculty includes outstanding investigators from UAB and MUSC (Institutional Research Base), as well as multiple institutions in the US and Canada (Extended Research Base). Each faculty member has a focused research effort in one of the Center's four thematic areas;1) cilia-related biology;2) regulation of epithelial transport;3) epithelial differentiation signaling pathways;and 4) matrix biology and fibrosis. To support and enhance innovative research efforts by these investigators, a set of four complementary Biomedical Research Cores that integrate existing intellectual and technological resources of UAB and MUSC are provided: 1) Core A: The Hepto/Renal Fibrocystic Diseases Translational Resource;2) Core B: The Engineered Models Resource;3) Core C: The Cellular Physiology Resource;and 4) Core D: The Immunoreagent and Structural Characterization Resource. In addition, three well-designed Pilot projects are proposed, each of which use novel approaches to address important mechanistic questions in hepato/renal fibrocystic diseases. An Educational Enrichment Program will facilitate interactions and enhance collaborative opportunities among the research base. Taken together, the Center Cores and the extraordinary cohort of assembled investigators will provide the breadth and depth of expertise that is critical for innovative and productive research. Significant added value comes from the Extended Research Base that includes both clinical and basic investigators, with this Core Center model accelerating the translation of new investigative insights toward new therapies for patients with hepato/renal fibrocystic diseases, particularly ARPKD. Public Health Relevance: The hepato/renal fibrocystic diseases are important causes of childhood morbidity and mortality. The UAB HRFDCC will apply state-of-the-art methodologies in a cost-effective manner to address experimental questions that will: 1) advance understanding disease pathogenesis, 2) enhance diagnostic specificity, and 3) facilitate new therapeutic approaches in the hepato/renal fibrocystic diseases, particularly ARPKD.